Analgesia is one of the most robust and best-studied placebo effects. Accumulated evidence indicates the existence of a spectrum of placebo analgesia mechanisms. Recent neuroimaging studies have demonstrated the involvement of multiple brain regions and neurotransmitters. Yet it is still unclear if the results from these experiments represent a general modality of the placebo effect or multiple distinct mechanisms elicited by specific situations. Mapping coherent and precise pathway(s) is an urgent challenge in placebo studies. The aim of this study is to generate preliminary innovative, high spatial resolution, simultaneous, multi-modal brain imaging data investigating precisely defined placebo analgesic effects in specific neurotransmitter system and whole brain activity as reflected by BOLD MR imaging. Specifically, based on evidence that placebo effects dependent on morphine conditioning are naloxone reversible, this proposal will investigate the brain mechanism of opioid (morphine) conditioning effects using innovative technology -- an integrated MRI-PET system that can collect fMRI and [11C] carfentanil PET data simultaneously. We believe this study (combined with an extended study planned for the future) will expand our understanding of drug-specific conditioning effects, addiction, mind-body interaction, and cognitive (conscious) and non-cognitive (unconscious) modulation processes on a more general level. PUBLIC HEALTH RELEVANCE: The aim of this study is to investigate the underlying mechanism of opioid (morphine) placebo effects using the innovative imaging technique of integrated MRI and PET.